Synergistic effects of azathioprine and ultraviolet light detected by sister chromatid exchange analysis.
The immunosuppressant azathioprine and longwave ultraviolet (UV) light have been postulated to have a synergistic effect on DNA resulting in carcinogenic change. This study investigated the in vitro effect of UV light on renal transplant recipients (RTRs) immunosuppressed with azathioprine and prednisolone to prevent rejection and patients on azathioprine for skin conditions and normal controls on no drug therapy. The results show clearly that there is an increase in sister chromatid exchanges (SCEs) in both patient groups in response to UV light with the greatest increase shown by the RTRs. Both patient groups without exposure to UV also showed a significant increase, as compared with normal controls, with the RTRs again showing the highest level. Both patient groups also showed disruption of the cell cycle in response to UV light as measured by the proliferative rate index (PRI) but the controls did not. These findings support the hypothesis of a synergistic effect between azathioprine and UV light and correlate well with the clinical pattern of carcinogenesis observed in these patients, with RTRs having a well-documented increased risk of neoplasia, particularly skin carcinomas in light-exposed areas.
Dalton
A
A
Department of Biochemistry, University of Sheffield, Western Bank, England.
Curtis
D
D
Harrington
C I
CI
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects*; D003043:Cocarcinogenesis; D004249:DNA Damage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012854:Sister Chromatid Exchange / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D001379:Azathioprine